The long-term objective of this project is to generate information useful for controlling aromatase action in breast cancer patients. Using immunocytochemistry and reverse transcriptation-polymerase chain reaction (RT-PCR), aromatase was found to be expressed in approximately 40% of the breast tumors examined. A nude mouse model with mice bearing aromatase-expressing tumors has been established. The clinical significance of in situ aromatization in breast cancer cells will be studied using such an in vivo model. The organization of the human aromatase gene will be investigated. The regulatory mechanism of aromatase expression in different aromatase expressing cells by hormones, and other reagents will also be investigated. The promoters and regulatory elements involved in regulating aromatase expression in breast cancer cells will be identified and characterized. In addition, site-directed mutagenesis and active site-labeling experiments will be applied to generate structural information at the active site region of aromatase. The information obtained can be used in the design of more effective treatment of breast cancer by aromatase inhibitors.